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Topic 4 ILC, Innate lymphoid cells

- What is ILC?
- Innate lymphoid cells are the innate counterparts to T cells. 
- They have similiar T cell functions but ==lack== the specific T cell receptor
- Why do we need ILCs if we have T cells?
    - ==Speed==: ILCs have rapid response, as a part of innate immunity. They respond immediately to alarm signals (such as cytokines)
    - ==Location==: ILCs are **tissue-resident** -- Which means it stationed at barrier surfaces like skin, gut, lungs; while naive T cells circulate through lymphoid organs and must be recruited to the tissue after infection starts
    - ==Specificity==: non-specific, which means it can response to any stress signals and cytokines
  • Classification
ILC Type Group T Cell Counterpart Primary Function
NK Cell Group 1 CD8+ CTL Cytotoxicity (Killing) 1111
ILC1 Group 1 Th1 Inflammation (IFN-$\gamma$) 2222
ILC2 Group 2 Th2 Immunity to parasites, allergy 3333
ILC3 Group 3 Th17 / Th22 Mucosal homeostasis (extracellular bacteria) 4444
LTi Cell Group 3 (None/Unique) Lymphoid Organogenesis (Building lymph nodes) 55
  • Group 1:
    • ==Activated== by IL-12, IL-18
    • ==regulated== by T-bet for ILC1, and Eomes for NK cell
    • ==release== IFN-$\gamma$ , TNF
    • NK cell
      • They are the innate counterpart to CD8+ Cytotoxic T Cells. Their primary job is cytotoxicity—killing infected or stressed cells directly using granules (perforin/granzymes).
      • Kill Mechanism:
        • the balance: NK cells have both ==activating receptors== (to kill) and ==inhibitory receptor== (not kill)
        • MHC Class I: healthy cells express MHC Class I --> bind inhibitory receptor of Nk cell
        • Missing MHC Class I: activating receptor --> kill this cell
  • Helper-like ILCs (ILC1, ILC2, ILC3)
    • These are the innate counterparts to CD4+ Helper T Cells (Th1, Th2, Th17). They primarily secrete cytokines to direct the immune response rather than killing cells directly.
  • Group 2:
    • ==Activated== by "Alarmins" from damaged epithelium: IL-25, IL-33, TSLP.
    • ==regulated== by GATA3
    • ==release== IL-4, IL-5, IL-13
  • Group 3:
    • Activated by IL-23, IL-1$\beta$
    • ==regulated== ROR$\gamma$
    • ==release== IL-17, Il-22
    • LTi are special; they are essential for the formation of secondary lymphoid organs (like lymph nodes and Peyer's patches) during development.

Plasticity of ILCs

  • ILCs can change their phenotypes in response to the environment
  • ILCs can switch their groups, examples
    • Crohn's Disease: helper-like ILC3s can transfer to inflammatory ILC1s
    • COPD: ILC2s can switch to ILC1s producing IFN-$\gamma$